Huntington's Disease (HD) is caused by expansion of the polyglutamine stretch in the widely expressed Huntingtin (HTT) protein. HD patients have motor, psychiatric, and cognitive changes due to changes in a variety of neural circuits. Somatostatin-expressing interneurons (SST-INs) can regulate neural circuits largely by inhibiting their target cells. Behaviorally, brain-wide inhibition of SST-INs increased anxiety in mice. Silencing striatal SST-INs caused a decrease in movement in the open field. Mutant HTT (mHTT) expressing mice exhibit abnormal motor, cognitive and psychiatric-like changes as well as electrophysiological changes in a variety of neurons, including striatal SST-INs. However, it is unknown whether cell autonomous expression of mHTT in SST-INs contributes to HD-associated behavioral phenotypes or causes abnormal electrophysiological changes in striatal SST-INs. To address these questions, we reduced mHTT expression in SST-INs throughout the brain of BACHD mice. Our findings show that brain-wide reduction of mHTT in SST-INs rescues anxiety-like behavior in male BACHD mice in the light-dark box, without improving performance in the open field or on the rotarod. Additionally, expression of mHTT in striatal SST-INs cell autonomously drives their increased excitability.
Fowler et al. (Fri,) studied this question.